{
  "abstract": "Phages have evolved various anti-CRISPR (Acr) proteins or RNA-based anti-CRISPR (Racr) to evade host CRISPR immunity by direct interference. However, whether other counter-CRISPR mechanisms exist remains unexplored. Here, we report a phage-encoded two-protein system, termed Healer, which neutralizes CRISPR immunity via a post-cleavage DNA repair mechanism. This phage replication-associated system comprises two proteins: Gp63 (a DUF669 domain-containing protein), and Gp64 (an AAA domain-containing protein). Mechanistic investigations elucidate that Gp63 acts as a rapid-response effector of CRISPR-induced DNA breaks. After Gp63 binds ssDNA, it promotes Gp64-mediated homologous recombination, which repairs CRISPR-generated phage DNA breaks and supports phage viability. Notably, co-expression of the Healer system with Cas9/Cas12 in E. coli, P. aeruginosa, and A. baumannii demonstrated high phage genome-editing efficiency. Collectively, our findings reveal an important anti-CRISPR complementary strategy, providing a promising tool for genome engineering.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.",
    "University of Chinese Academy of Sciences, Beijing, China.",
    "Department of Biochemistry, School of Medicine, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, China.",
    "State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. nan.li@siat.ac.cn.",
    "State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. yingfei.ma@siat.ac.cn.",
    "University of Chinese Academy of Sciences, Beijing, China. yingfei.ma@siat.ac.cn."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Heng Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengkun Dai",
      "orcid": "0000-0001-5345-7053"
    },
    {
      "affs": [
        0
      ],
      "name": "Hewen Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Shifeng Hou"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuelong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin Tan"
    },
    {
      "affs": [
        2
      ],
      "name": "Ning Jia",
      "orcid": "0000-0002-0672-454X"
    },
    {
      "affs": [
        3
      ],
      "name": "Nan Li",
      "orcid": "0000-0002-7121-7579"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Yingfei Ma",
      "orcid": "0000-0002-2563-5390"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4a6k2h1m9t75d.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77998-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13687109",
  "id": "4a6k2h1m9t75d",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907433",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7125283149",
  "pdf_url": "https://europepmc.org/articles/PMC13687109?pdf=render",
  "pmcid": "PMC13687109",
  "pmid": "42907433",
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4a6k2h1m9t75d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907433",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907433"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|CRISPR and Genetic Engineering",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A phage DUF669 protein mediates post-cleavage DNA repair against host CRISPR immunity.",
  "title_text": "A phage DUF669 protein mediates post-cleavage DNA repair against host CRISPR immunity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/4a6k2h1m9t75d",
  "venue": "Nature communications",
  "versions": []
}